Role of nitroreduction in the synergistic mutational response induced by mixtures of 1- and 3- nitrobenzo[a]pyrene inSalmonella typhimurium

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Abstract
Previous studies showed that binary mixtures of the environmental pollutants 1‐ and 3‐nitrobenzo[a]pyrene produced a synergistic mutational response in the Salmonella reversion assay. Since nitroreduction is believed to mediate the direct‐acting mutagenicity of the individual compounds, we have examined the role of nitroreduction in the mutagenicity of mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene in the Salmonella plate incorporation assay. While mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene induced up to 183% more revertants in strain TA98 than produced by equivalent amounts of the individual compounds, in the nitroreductase‐deficient strain TA98NR the same mixtures only induced up to 57% more revertants than the individual compounds. Analysis of mixtures of 1 ‐ and 3‐nitrosobenzo[a]pyrene (the two‐electron reduction products of 1 ‐ and 3‐nitrobenzo[a]pyrene) for mutation induction in TA98 yielded no evidence of a synergistic effect between the compounds. The mutagenicity of the mixtures was dependent upon the amount of the more mutagenic component. Salmonella cultures were also incubated with mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene, as well as with equivalent amounts of the individual compounds. In two experiments, nitroreductive ability, as measured by the amount of 1 ‐nitropyrene metabolized to 1 ‐aminopyrene in 1 hr, was increased 9 to 105% in cultures pretreated with the mixtures as compared with cultures pretreated with the individual compounds. The results of this study support the hypothesis that nitroreduction is a major factor in the synergistic mutational response induced by 1 ‐ and 3‐nitrobenzo[a]pyrene in Salmonella typhimurium.

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